Chemical synapses exhibit various forms of short-term plasticity that determine what information they transmit to downstream circuits. Although the molecular mechanisms underlying this plasticity have been studied extensively, its consequences for circuit function and behavior are unclear. Here we propose to use the first olfactory relay of Drosophila as a model to understand the computational and behavioral consequences of short-term synaptic plasticity. Recently we found that each major synapse type in this circuit exhibits distinct forms of short-term plasticity. We developed a computational model that relates plasticity at these synapses to the ability of the circuit to encode fluctuating odor stimuli, such as the odor plumes a fly encounters in the natural world. In preliminary results, we have shown that we can use genetic manipulations to alter the dynamics of synaptic transmission at particular synapse types. In addition, we have developed a behavioral paradigm that allows us to measure behavioral responses to fluctuating odors with high temporal precision. We will leverage the powerful genetic tools available in Drosophila to manipulate short-term plasticity specifically at each synapse type in this circuit, and to measure the consequences of these manipulations for sensory encoding and behavior. We will compare the experimental effects of these manipulations to the predictions of our computational model. These experiments will allow us to quantitatively assess the contribution of synaptic processes to sensory coding and behavior, and will provide insight into the effects of synaptic perturbations in disease states.
A common feature of many psychiatric disease states is an inability to process ongoing sensory stimuli. A current hypothesis suggests that many of these diseases may arise from subtle synaptic defects that do not prevent synaptic transmission, but do interfere with normal synaptic plasticity. We are using the model organism Drosophila to investigate the sensory and behavioral consequences of perturbed synaptic function.
| Fulterer, Andreas; Andlauer, Till F M; Ender, Anatoli et al. (2018) Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses. Cell Rep 23:1259-1274 |
| Álvarez-Salvado, Efrén; Licata, Angela M; Connor, Erin G et al. (2018) Elementary sensory-motor transformations underlying olfactory navigation in walking fruit-flies. Elife 7: |
